biostudies-literatureSermersheim MU.S. Department of Health & Human Services | NIH | National Institute of General Medical SciencesNIDDK NIH HHSNIAID NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious DiseasesNHLBI NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin DiseasesU.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood InstituteNIAMS NIH HHSNIGMS NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases3624https://www.ebi.ac.uk/biostudies/studies/S-EPMC7368064biostudies-literatureUnknown11(1)TRIM family proteins play integral roles in the innate immune response to virus infection. MG53 (TRIM72) is essential for cell membrane repair and is believed to be a muscle-specific TRIM protein. Here we show human macrophages express MG53, and MG53 protein expression is reduced following virus infection. Knockdown of MG53 in macrophages leads to increases in type I interferon (IFN) upon infection. MG53 knockout mice infected with influenza virus show comparable influenza virus titres to wild type mice, but display increased morbidity accompanied by more accumulation of CD45+ cells and elevation of IFNβ in the lung. We find that MG53 knockdown results in activation of NFκB signalling, which is linked to an increase in intracellular calcium oscillation mediated by ryanodine receptor (RyR). MG53 inhibits IFNβ induction in an RyR-dependent manner. This study establishes MG53 as a new target for control of virus-induced morbidity and tissue injury.Nature communicationsMG53 suppresses interferon-β and inflammation via regulation of ryanodine receptor-mediated intracellular calcium signaling.PMC7368064DK106394R01 HL157215R21 AI146690GM068412R21 AI142256HL138570R01 DK106394AI142256R01 AR061385R01 AI130110AR070752R01 HL138570AR061385T32 GM068412AI130110R01 AR070752Li HYount JSMcMichael TMCai CGumpper KPark KHAdesanya TMAKenney ADMa JLin PHZhou XSermersheim MfalseMG53 suppresses interferon-β and inflammation via regulation of ryanodine receptor-mediated intracellular calcium signaling.TRIM family proteins play integral roles in the innate immune response to virus infection. MG53 (TRIM72) is essential for cell membrane repair and is believed to be a muscle-specific TRIM protein. Here we show human macrophages express MG53, and MG53 protein expression is reduced following virus infection. Knockdown of MG53 in macrophages leads to increases in type I interferon (IFN) upon infection. MG53 knockout mice infected with influenza virus show comparable influenza virus titres to wild type mice, but display increased morbidity accompanied by more accumulation of CD45+ cells and elevation of IFNβ in the lung. We find that MG53 knockdown results in activation of NFκB signalling, which is linked to an increase in intracellular calcium oscillation mediated by ryanodine receptor (RyR). MG53 inhibits IFNβ induction in an RyR-dependent manner. This study establishes MG53 as a new target for control of virus-induced morbidity and tissue injury.2020-01-01T00:00:00Z2020 Jul2026-07-09T10:34:17.958Z2025-04-06T02:48:12.152ZS-EPMC73680643268103610.1038/s41467-020-17177-6